Cancer Therapies

Dendritic Cell-Based Therapy for Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most malignant brain tumour, accounting for 60–70% of all gliomas, with a very high mortality rate. Death occurs in a large proportion of GBM patients within 3 years, however we are observing patients that are living 5 years and beyond. The current gold-standard first-line treatment is maximal safe resection combined with radiotherapy and temozolomide chemotherapy. However, surgical resection is usually incomplete because of tumor cells infiltration into the brain parenchyma. This is what causes tumor relapse. It has been estimated that the median survival time is 12–15 months in primary GBM patients treated with conventional treatment (surgery, chemotherapy, and radiation) and survival is 15-20% for 6 months in patients with GBM recurrence.

The body has its own immune surveillance system for its defense against external and internal insults (known as inborn resistance or immunity). This gets either inactivated or masked by the cancers hence we cannot destroy the cancer once it has grown to a certain size. The balance between the production of cancer cells and destruction by the body’s immune response can be restored by activating certain cells including Dendritic Cells (DCs).

Research has, therefore, focused on novel treatments for the improvement of GBM outcomes. Immunotherapy could possibly be a successful treatment option with the advantage of high tumor-specific targeting method of harnessing the power of the host immune system by inducing, enhancing, or suppressing immune responses to reject cancer cells. This concept is becoming an increasingly attractive therapeutic option in oncology.

Dendritic cells (DCs) are the most powerful human antigen presenting cells (APCs) to the body’s natural defense system-the immune surveillance system. DC-based vaccines have the potential to improve clinical outcomes by enhancing GBM cell responses to existing therapy and/or stimulating innate (pre-existing) immune responses with minimal toxicity. Active immunotherapy includes promoting an immune response through tumor vaccines. Given as a vaccine, APCs can effectively be loaded with tumor derived antigens that will accelerate tumor eradication within in vivo settings and enhance recognition of GBM cells by the patients’ immune system. This leads to an increased activity of tumor-infiltrating lymphocytes (TILs) against them, creating potent, long-lasting tumor-specific T lymphocytes that can successfully kill GBM cells. On the other hand, passive immunotherapy induces an antitumor effect by transferring effector immune cells into patients.

DCs are granular lymphocytes with high cell surface markers: major histocompatibility complex (MHC) class I molecules, MHC class II molecules, and CD86 that are involved in both innate and adaptive immune systems. They also display various characteristics in immune regulatory systems that balance the complex system of inflammatory and inhibitory immune reactions in the tumor microenvironment.

In GBM, DCs activate T-cells slowly generating a longer and more sustained T-cell response. Autologous DCs exposed to GBM-associated antigens take up and process the antigens as peptides on their cell surface and are injected back into patients as a vaccine therapy. Presently the DCs are being tested in clinical trials to determine the efficacy and response against many cancers including the Glioblastoma multiforme.